The balance of serum matrix metalloproteinase-8 and its tissue inhibitor in acute coronary syndrome and its recurrence

Background: Matrix metalloproteinase-8 (MMP-8) is involved in the breakdown of the extracellular matrix increasing the vulnerability of atherosclerotic lesions. We analysed the diagnostic value of serum MMP-8 and tissue inhibitor of metalloproteinase-1 (TIMP-1) concentrations in acute coronary syndrome (ACS) and their prognostic value in ACS recurrence. Methods: The population comprised 343 patients with ACS [including 108 unstable angina pectoris and 235 acute myocardial infarctions (AMI)] and 326 healthy controls. Additionally, 157 (45.8%) patients were resampled during the recovery. The ACS patients were followed up for 6 years. Results: MMP-8, TIMP-1, and their molar ratio distinguished the cases from the controls; C-statistic of the multivariate model (95% CI, p-value) including the MMP-8/TIMP-1 ratio regarding its discriminating ability for AMI was 0.922 (0.893-0.950, p < 0.001). After the acute phase of ACS, median MMP-8 and TIMP-1 concentrations decreased (p < 0.001) by 34.5 and 28.7%, respectively, but ended up on a different level than those found in the controls. In the follow-up, acute phase and recovery period TIMP-1 concentrations associated with cardiovascular death with hazard ratios 4.31 (2.00-9.26, p < 0.001) and 4.69 (1.10-20.01, p = 0.037), respectively. Conclusions: The increase of serum MMP-8 and TIMP-1 concentrations may reflect plaque instability and tissue damage. TIMP-1 concentrations are associated with poor outcome in patients with ACS. The findings may have practical implications in both diagnostics and therapeutics. (c) 2011 Elsevier Ireland Ltd. All rights reserved

Resistance to aspirin is increased by ST-elevation myocardial infarction and correlates with adenosine diphosphate levels

BACKGROUND: To be fully activated platelets are dependent on two positive feedback loops; the formation of thromboxane A(2 )by cyclooxygenase in the platelets and the release of ADP. We wanted to evaluate the effect of aspirin on platelet function in patients with acute coronary syndromes and we hypothesized that increased levels of ADP in patients with acute coronary syndromes could contribute to aspirin resistance. METHODS: Platelet activity in 135 patients admitted for chest pain was assessed with PFA-100. An epinephrine-collagen cartridge (EPI-COLL) was used for the detection of aspirin resistance together with an ADP-collagen cartridge (ADP-COLL). ADP was measured with hplc from antecubital vein samples. Three subgroups were compared: chest pain with no sign of cardiac disease (NCD), NonST-elevation myocardial infarction (NSTEMI) and STEMI. RESULTS: Platelet activation was increased for the STEMI group compared NCD. Aspirin resistance defined as <193 sec in EPI-COLL was 9.7 % in NCD, and increased to 26.0 % (n.s.) in NSTEMI and 83.3 % (p < 0.001) in STEMI. Chronic aspirin treatment significantly reduced platelet aggregation in NCD and NSTEMI, but it had no effect in STEMI. Plasma levels of ADP were markedly increased in STEMI (905 ± 721 nmol/l, p < 0.01), but not in NSTEMI (317 ± 245), compared to NCD (334 ± 271, mean ± SD). ADP levels correlated with increased platelet activity measured with ADP-COLL (r = -0.30, p < 0.05). Aspirin resistant patients (EPI-COLL < 193 sec) had higher ADP levels compared to aspirin responders (734 ± 807 vs. 282 ± 187 nmol/l, mean ± SD, p < 0.05). CONCLUSION: Platelets are activated and aspirin resistance is more frequent in STEMI, probably due to a general activation of platelets. ADP levels are increased in STEMI and correlates with platelet activation. Increased levels of ADP could be one reason for increased platelet activity and aspirin resistance

Infarct evolution in man studied in patients with first-time coronary occlusion in comparison to different species - implications for assessment of myocardial salvage

<p>Abstract</p> <p>Background</p> <p>The time course of infarct evolution, i.e. how fast myocardial infarction (MI) develops during coronary artery occlusion, is well known for several species, whereas no direct evidence exists on the evolution of MI size normalized to myocardium at risk (MaR) in man. Despite the lack of direct evidence, current literature often refers to the "golden hour" as the time during which myocardial salvage can be accomplished by reperfusion therapy. Therefore, the aim of the present study was to investigate how duration of myocardial ischemia affects infarct evolution in man in relation to previous animal data. Consecutive patients with clinical signs of acute myocardial ischemia were screened and considered for enrollment. Particular care was taken to assure uniformity of the patients enrolled with regard to old MI, success of revascularization, collateral flow, release of biochemical markers prior to intervention etc. Sixteen patients were ultimately included in the study. Myocardium at risk was assessed acutely by acute Myocardial Perfusion Single photon emission computed tomography (MPS) and by T2 imaging (T2-STIR) cardiovascular magnetic resonance (CMR) after one week in 10 of the 16 patients. Infarct size was measured by late gadolinium enhancement (LGE) at one week.</p> <p>Results</p> <p>The time to reach 50% MI of the MaR (T₅₀) was significantly shorter in pigs (37 min), rats (41 min) and dogs (181 min) compared to humans (288 min). There was no significant difference in T₅₀when using MPS compared to T2-STIR (p = 0.53) for assessment of MaR (288 ± 23 min vs 310 ± 22 min, T₅₀± standard error). The transmural extent of MI increased progressively as the duration of ischemia increased (R²= 0.56, p < 0.001).</p> <p>Conclusion</p> <p>This is the first study to provide direct evidence of the time course of acute myocardial infarct evolution in relation to MaR in man with first-time MI. Infarct evolution in man is significantly slower than in pigs, rats and dogs. Furthermore, infarct evolution assessments in man are similar when using MPS acutely and T2-STIR one week later for determination of MaR, which significantly facilitates future clinical trials of cardioprotective therapies in acute coronary syndrome by the use of CMR.</p

Assessing left ventricular systolic function in shock: evaluation of echocardiographic parameters in intensive care

Introduction: Assessing left ventricular (LV) systolic function in a rapid and reliable way can be challenging in the critically ill patient. The purpose of this study was to evaluate the feasibility and reliability of, as well as the association between, commonly used LV systolic parameters, by using serial transthoracic echocardiography (TTE). Methods: Fifty patients with shock and mechanical ventilation were included. TTE examinations were performed daily for a total of 7 days. Methods used to assess LV systolic function were visually estimated, "eyeball" ejection fraction (EBEF), the Simpson single-plane method, mean atrioventricular plane displacement (AVPDm), septal tissue velocity imaging (TDIs), and velocity time integral in the left ventricular outflow tract (VTI). Results: EBEF, AVPDm, TDIs, VTI, and the Simpson were obtained in 100%, 100%, 99%, 95% and 93%, respectively, of all possible examinations. The correlations between the Simpson and EBEF showed r values for all 7 days ranging from 0.79 to 0.95 (P < 0.01). the Simpson correlations with the other LV parameters showed substantial variation over time, with the poorest results seen for TDIs and AVPDm. The repeatability was best for VTI (interobserver coefficient of variation (CV) 4.8%, and intraobserver CV, 3.1%), and AVPDm (5.3% and 4.4%, respectively), and worst for the Simpson method (8.2% and 10.6%, respectively). Conclusions: EBEF and AVPDm provided the best, and Simpson, the worst feasibility when assessing LV systolic function in a population of mechanically ventilated, hemodynamically unstable patients. Additionally, the Simpson showed the poorest repeatability. We suggest that EBEF can be used instead of single-plane Simpson when assessing LV ejection fraction in this category of patients. TDIs and AVPDm, as markers of longitudinal function of the LV, are not interchangeable with LV ejection fraction

A simple statistical model for prediction of acute coronary syndrome in chest pain patients in the emergency department

BACKGROUND: Several models for prediction of acute coronary syndrome (ACS) among chest pain patients in the emergency department (ED) have been presented, but many models predict only the likelihood of acute myocardial infarction, or include a large number of variables, which make them less than optimal for implementation at a busy ED. We report here a simple statistical model for ACS prediction that could be used in routine care at a busy ED. METHODS: Multivariable analysis and logistic regression were used on data from 634 ED visits for chest pain. Only data immediately available at patient presentation were used. To make ACS prediction stable and the model useful for personnel inexperienced in electrocardiogram (ECG) reading, simple ECG data suitable for computerized reading were included. RESULTS: Besides ECG, eight variables were found to be important for ACS prediction, and included in the model: age, chest discomfort at presentation, symptom duration and previous hypertension, angina pectoris, AMI, congestive heart failure or PCI/CABG. At an ACS prevalence of 21% and a set sensitivity of 95%, the negative predictive value of the model was 96%. CONCLUSION: The present prediction model, combined with the clinical judgment of ED personnel, could be useful for the early discharge of chest pain patients in populations with a low prevalence of ACS

Episka liknelser i Iliaden och Odysséen

Ämnet för uppsatsen är episka liknelser i Iliaden och Odysséen. Med episka liknelser avses liknelser som återger ett skeende och inte bara ett objekt och dess egenskaper. Frekvensen av episka liknelser och motiven för liknelserna undersökes i båda verken. Vidare studeras vilka liknelser som har ett destruktivt innehåll. Ytterligare en frågeställning i uppsatsen är hur applicerbar Lakoffs och Johnsons metaforteori är på den episka liknelserna i de båda verken

Perspectives that lay persons with and without health problems show toward coronary heart disease: An integrated biopsychosocial approach.

Objective: We studied what patients with acute coronary heart disease (CHD) considered the three most stressful factors experienced during the month before testing and what they attributed their heart disease to. Methods: We studied the occurrence and severity of physiologic, psychologic, and psychosocial stressors in 117 patients with acute CHD and 117 referents, not diagnosed with CHD, matched by age,, sex, and municipality. The subjects were first to select the factors they considered stressful from a list of potentially stressful factors. They were then to select the three they regarded as most stressful and to provide situational accounts of these. Results: The patients with CHD were found to less frequently live with a partner, to more frequently have a body mass index higher than 30.0, and to report a greater number of stressors. The stressors best differentiating them from the referents were fatigue, shortness of breath, pain, and high blood pressure. The causal factors they most frequently named were heart problems, smoking, heredity, high workload, and poor eating habits. Conclusions: The situational accounts the patients provided illustrate the biopsychosocial complexities involved in the various categories of stressful factors

Lipid peroxidation is not increased in heart failure patients on modern pharmacological therapy.

Background: Previous studies support a role of oxygen-free radicals in the development of congestive heart failure (CHF). The aim of this study was to investigate whether lipid peroxidation is increased in CHF patients on modem pharmacological therapy and whether there is a positive correlation between plasma levels of markers of lipid peroxidation and severity of heart failure (HF). Plasma malondialdehyde (MDA) and isoprostanes are often used as markers of lipid peroxidation and oxidative stress. We also studied whether long-term treatment with isosorbide-5-mononitrate (IS-5-MN) in combination with standard HF therapy affects P-MDA levels in patients with evidence of left ventricular (LV) dysfunction following acute myocardial infarction (AMI). Materials and methods: Ninety-two patients with clinical or echocardiographic evidence of LV-dysfunction following AMI were randomized to treatment with either IS-5-MN or placebo. In a subgroup of 83 patients with available plasma MDA, echocardiography, right-heart catherization, and plasma natriuretic peptides were evaluated. Control subjects were 80 healthy blood donors. A second study group consisted of 56 patients with CHF, evaluated with respect to LV function, brain natriuretic peptide and markers of oxidative stress (P-MDA and 8-isoprostane). The second control group comprised 50 healthy subjects. Results: Lipid peroxidation measured by P-MDA and 8-isoprostane was not increased in patients with LV dysfunction treated with standard HF therapy. No positive correlation was found to the severity of HE Long-term IS-5-MN therapy did not influence P-MDA concentrations. Conclusions: Although results from many experimental and clinical studies suggest that oxidative stress is increased in HF, this may not be true for patients treated with beta blockers and inhibitors of the renin-angiotensin system. (c) 2005 Elsevier Ireland Ltd. All rights reserved